Abstract
Growth hormona (GH) secretory responses to provocative stimulation tests are often blunted in short statured children. The objective of the present study was to evaluate various pituitary factors that may contribute to low GH secretion using rodent models that are hyporesponaive to GH secretagogues. Plasma GH concentrations did not increase above basal values (1.7 ± 0.7 vs 316 ± 89.9 ng/ml) after GHRH and/or GHRP administration in mice lacking pituitary receptors for GH. Plasma GH increased in dwarf rats with defective cAMP second messenger systems; however, concentrations were lower than normal (67 ± 3 ng/ml vs 1396 ± 76 ng/ml; p < 0.001). Stimulated GH secretion in old rats administered GHRH or GHRP was significantly lower than in young rats (393 ± 69 ng/ml vs 1477 ± 111 ng/ml; p < 0.01), whereas plasma GH concentrations were comparable in both age groups administered GHRH and GHRP (1079 ± 106 ng/ml vs 1159 ± 93 ng/ml). Chronic coadministration of GHRH and GHRP to old rats also restored youthful patterns of GH secretion, increased pituitary GH concentrations (7 ± 2 μg/mg vs 51 ± 9 μg/mg; p < 0.001) and increased serum IGF-1 (413 ± 77 ng/ml vs 810 ± 82 ng/ml). These data suggest that blunted responses to provocative GH releasing stimuli result from defects in pituitary receptors, second messengers and/or to inadequate pituitary stimulation; each with different effects on GH secretion. Receptor defects completely blocked and second messenger defects partially blocked GH secretory stimuli, whereas inadequately stimulated pituitaries gave differential responses to GH releasing peptides. Thus, by comparing responses to lone and paired GH secretagogues it may be possible to discern the etiology of GH secretory deficits in certain short statured children. When GH secretory deficiency results from inadequate pituitary stimulation, co-administration of GH secretagogues may restore proper GH secretion as well as increase pituitary GH stores and serum IGF-1 concentrations.
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Bercu, B., Walker, R. ANALYSIS OF GROWTH HORMONE SECRETORY DEFICIENCY IN RODENT MODELS. Pediatr Res 33 (Suppl 5), S48 (1993). https://doi.org/10.1203/00006450-199305001-00269
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DOI: https://doi.org/10.1203/00006450-199305001-00269